1. Field of the Invention
The present invention relates to a sample-introduction tool for introducing a sample solution into an analyzer or for melting a frozen sample with a solvent and introducing the melted sample into an analyzer. More particularly, the invention relates to a small sample-introduction tool which is formed on a substrate made of silicon or quartz and can continuously introduce a small amount of samples at high speed. The invention also relates to a mass spectrometer which can be connected to the sample-introduction tool.
2. Description of the Related Arts
A capillary electrophoresis apparatus (CE) and a liquid chromatograph (LC) can separate a sample substance dissolved in a solution but it is hard for them to identify the kind of a separated sample substance. On the other hand, a mass spectrometer (MS) can identify a sample substance with high sensitivity, but cannot separate a sample substance dissolved in a solution. In the case of separating and analyzing a plurality of sample substances dissolved in a solvent such as water, capillary electrophoresis/mass spectrometer (CE/MS) in which a capillary electrophoresis apparatus is coupled to a mass spectrometer or liquid chromatograph/mass spectrometer (LC/MS) in which a liquid chromatograph is coupled to a mass spectrometer is generally used.
The CE/MS is described in xe2x80x9cAnalytical Chemistryxe2x80x9d, 60, pp. 436-441 (1988).
A technique of forming a narrow groove on a glass substrate and performing electrophoresis via the groove to thereby separate mixed samples from each other is described in xe2x80x9cAnalytical Chemistryxe2x80x9d, 65, pp. 2637-2642 (1993).
In order to analyze a sample substance separated by the capillary electrophoresis apparatus or liquid chromatograph by a mass spectrometer, it is necessary to transform the sample molecules in the solution to gaseous ions. Known conventional techniques for obtaining such gaseous ions are ion spray ionization (Analytical Chemistry, 59, pp. 2642-2646 (1987)), the electro spray ionization (Journal of Physical Chemistry, 88, pp. 4451-4459 (1984)), atmospheric pressure ionization (Analytical Chemistry, 54, pp. 143-146 (1982)), and the like.
As ionization different from the above conventional techniques, sonic spray ionization capable of efficiently generating gaseous ions only by spraying a sample solution by a sonic gas stream has been recently reported (Analytical Chemistry, 66, pp. 4557-4559 (1994), Analytical Chemistry, 67, pp. 2878-2882 (1995), and Japanese Unexamined-Patent Application Nos. 07-306193 and 08-062200). In the ionization, it is considered that small charged droplets are generated by a sonic gas stream and solvent molecule are peeled off from the charged droplets, thereby generating gaseous ions of the sample molecules.
A method of continuously introducing a small amount of samples by gravity without using a liquid chromatography or a solution sending pump at the time of introducing a sample into the mass spectrometer is disclosed in Japanese Unexamined Patent Application No. 08-005624. Further, a capillary electrophoresis/mass spectrometer which eliminates the need for providing a solution sending pump of a nebulization auxiliary solution by applying the sonic spray ionization to an ion source is disclosed in Japanese Unexamined Patent Application No. 09-243600.
In the case of introducing a sample solution to an analyzer such as a liquid chromatograph/mass spectrometer (LC/MS), a method of injecting a sample to a passage through which a mobile phase solution is flowing by a pump or the like connected to a syringe or autosampler is conventionally used. A sample-introduction passage to which a syringe is fit or a sample-introduction passage of the autosampler is branched from a mobile phase passage, and the flow of a solution is switched by a valve or the like. Since the valve is in contact with the sample solution, it is apt to be unclean and it often causes what is called contamination in which a sample component introduced last time is mixed with a sample of this time. Since it is necessary to switch the valve, inject samples, and again switch the valve for each sample introduction, in the case of analyzing a number of kinds of samples, it takes very long time.
In the case of using a mass spectrometer as an analyzer of an introduced sample, the inside of the mass spectrometer is not resistive to contamination and the sensitivity deteriorates when it becomes contaminated, so that the inside of the mass spectrometer has to be periodically cleaned. Consequently, in the conventional sample introducing method, it is difficult to perform analysis continuously for long time. In order to clean the inside of the mass spectrometer, the inside of the mass spectrometer which is kept in vacuum during analysis has to be exposed to atmosphere, so that it takes long time to re-obtain a degree of vacuum at which analysis can be performed. When the interval of cleaning is short, a problem such that analysis throughput considerably deteriorates arises.
It is, therefore, an object of the invention to provide a sample-introduction tool capable of continuously or intermittently introducing samples into a solution of constant flow velocity without requiring a valve for switching a passage to prevent contamination as described above and capable of improving analysis throughput by shortening time required to introduce samples.
Another object of the invention is to provide a mass spectrometer which can be connected to the sample-introduction tool according to the invention and can conduct high-speed analysis on a sample introduced at high speed.
When a mobile phase solution is sent by applying pressure to the passage inlet by a pump or the like and a sample is also introduced by applying pressure as in a conventional manner, if the passage is not switched to pass the solution only to one of the passages, the solution flows backward to the other passage. Consequently, a passage switching valve is necessary. In the present invention, the pressure on the outlet side of the passage is reduced and the solution is pumped by the pressure difference between the reduced pressure and the pressure on the passage inlet side. With such a construction, even when a sample-introduction passage is branched from a passage and a valve is not provided at the branch, the solution does not flow backward. Further, even when an end portion of the sample-introduction passage is opened, the mobile phase solution does not flow backward, so that samples can be sequentially charged while the end portion of the sample-introduction passage remains open. Thus, analysis throughput can be improved.
In order to minimize contamination in the mass spectrometer and reduce the number of cleaning times so that analysis can be conducted for long time, the amount of a sample has to be minimized. For this purpose, a passage through which a solution flows is formed on a substrate by micromachining and the system itself is miniaturized.